Tumor Cell-Secreted ISG15 Promotes Tumor Cell Migration and Immune Suppression by Inducing the Macrophage M2-Like Phenotype.
Tumor Cell-Secreted ISG15 Promotes Tumor Cell Migration and Immune Suppression by Inducing the Macrophage M2-Like Phenotype.
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肿瘤细胞分泌的ISG15通过诱导巨噬细胞M2样表型促进肿瘤细胞迁移和免疫抑制
DOI：
10.3389/fimmu.2020.594775
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发表时间：
2020
影响因子：
7.3
通讯作者：
Huang XM
中科院分区：
文献类型：
--
作者：
Chen RH;Xiao ZW;Yan XQ;Han P;Liang FY;Wang JY;Yu ST;Zhang TZ;Chen SQ;Zhong Q;Huang XM
干扰素刺激基因15（ISG 15）被认为与肿瘤进展有关。我们曾报道ISG 15在鼻咽癌细胞上表达，并与鼻咽癌患者预后不良有关。我们进一步观察到ISG 15可以由NPC细胞分泌并在巨噬细胞上原位表达。然而，ISG 15在肿瘤相关巨噬细胞（TAM）中的作用仍然知之甚少。在本研究中，我们发现ISG 15处理诱导巨噬细胞具有M2样表型，并增强NPC细胞的迁移和致瘤性。在机械上，ISG 15诱导的M2样表型依赖于与其受体LFA-1的相互作用，SRC家族激酶（SFK）信号的参与，以及随后的CCL 18分泌。用小分子抑制剂阻断LFA-1或SRC信号，或用抗CCL 18抗体中和可阻碍ISG 15处理的巨噬细胞中LFA-1-SFK-CCL 18轴的活化。临床上，ISG 15 + CD 163 + TAMs与NPC患者的生存受损和晚期肿瘤分期有关。此外，我们发现ISG 15 + CD 163+巨噬细胞抑制NPC中的抗肿瘤CD 8+细胞反应。总之，我们的研究结果表明，肿瘤细胞分泌的ISG 15作为肿瘤微环境因子，诱导M2样表型，促进肿瘤进展和抑制细胞毒性T淋巴细胞反应。
Interferon-stimulated gene 15 (ISG15) is known to be involved in tumor progression. We previously reported that ISG15 expressed on nasopharyngeal carcinoma (NPC) cells and related to poor prognosis of patients with NPC. We further observed that ISG15 can be secreted by NPC cell and expressed on the macrophages in situ. However, the role of ISG15 in tumor-associated macrophages (TAMs) remains poorly understood. In the present study, we found that ISG15 treatment induces macrophages with M2-like phenotype, and the enhancement of NPC cell migration and tumorigenicity. Mechanically, ISG15-induced M2-like phenotype is dependent on the interaction with its receptor, LFA-1, and engagement of SRC family kinase (SFK) signal, and the subsequent secretion of CCL18. Blocking LFA-1, or SRC signal with small molecular inhibitors, or neutralizing with anti-CCL18 antibody can impede the activation of LFA-1-SFK-CCL18 axis in ISG15-treated macrophages. Clinically, ISG15+ CD163+ TAMs related to impaired survival of patients and advanced tumor stage of NPC. Furthermore, we found ISG15+ CD163+ macrophages inhibited antitumor CD8+ cells responses in NPC. Together, our findings suggested tumor cell-secreted ISG15, which acted as a tumor microenvironmental factor, induces M2-like phenotype, promoting tumor progression and suppression of cytotoxic T lymphocyte response.
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ISG15预测鼻咽癌不良预后并促进癌症干细胞表型
影响因子：
--
作者：
Chen RH;Du Y;Han P;Wang HB;Liang FY;Feng GK;Zhou AJ;Cai MY;Zhong Q;Zeng MS;Huang XM
通讯作者：
Huang XM
影响因子：
37.3
作者：
Lane D;Matte I;Laplante C;Garde-Granger P;Carignan A;Bessette P;Rancourt C;Piché A
通讯作者：
Piché A
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Zhang, Xianqin;Bogunovic, Dusan;Payelle-Brogard, Beatrice;Francois-Newton, Veronique;Speer, Scott D.;Yuan, Chao;Volpi, Stefano;Li, Zhi;Sanal, Ozden;Mansouri, Davood;Tezcan, Ilhan;Rice, Gillian I.;Chen, Chunyuan;Mansouri, Nahal;Mahdaviani, Seyed Alireza;Itan, Yuval;Boisson, Bertrand;Okada, Satoshi;Zeng, Lu;Wang, Xing;Jiang, Hui;Liu, Wenqiang;Han, Tiantian;Liu, Delin;Ma, Tao;Wang, Bo;Liu, Mugen;Liu, Jing-Yu;Wang, Qing K.;Yalnizoglu, Dilek;Radoshevich, Lilliana;Uze, Gilles;Gros, Philippe;Rozenberg, Flore;Zhang, Shen-Ying;Jouanguy, Emmanuelle;Bustamante, Jacinta;Garcia-Sastre, Adolfo;Abel, Laurent;Lebon, Pierre;Notarangelo, Luigi D.;Crow, Yanick J.;Boisson-Dupuis, Stephanie;Casanova, Jean-Laurent;Pellegrini, Sandra
通讯作者：
Pellegrini, Sandra
DOI：
10.1126/science.1224026
发表时间：
2012-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bogunovic D;Byun M;Durfee LA;Abhyankar A;Sanal O;Mansouri D;Salem S;Radovanovic I;Grant AV;Adimi P;Mansouri N;Okada S;Bryant VL;Kong XF;Kreins A;Velez MM;Boisson B;Khalilzadeh S;Ozcelik U;Darazam IA;Schoggins JW;Rice CM;Al-Muhsen S;Behr M;Vogt G;Puel A;Bustamante J;Gros P;Huibregtse JM;Abel L;Boisson-Dupuis S;Casanova JL
通讯作者：
Casanova JL